Megakaryocyte growth in vitro predicts outcome in idiopathic thrombocytopenic purpura.

Purpose: The impact of megakaryocyte growth in vitro on clinical data, especially outcome, was studied in 25 consecutive children with idiopathic thrombocytopenic purpura (ITP).

Patients and methods: Twenty children with untreated de novo ITP and five children with pretreated ITP were evaluated. The number of megakaryocyte colonies (cloning efficiency), the mean cell number per colony (mitotic amplification) and the percentages of polyploid megakaryocytes after 7 and 12 days in culture (relative size of the endomitotic compartment) were determined in two separate clonal assays. The culture data were related to clinical findings and outcome of the thrombocytopenia.

Results: The mean cell number per megakaryocyte colony was significantly correlated with the observed increase in the platelet count 5 days after starting therapy (n = 23; r = 0.642), and a significant negative correlation was found between the relative size of the endomitotic compartment and the duration of thrombocytopenia after bone marrow culture analysis (n = 25; r = -0.503). If all 25 children with ITP (untreated de novo and pretreated ITP) were considered, a normal frequency of polyploid megakaryocytes was associated with a duration of ITP for < 6 months in 14 of 16 cases, whereas an impaired polyploidization predicted a persistence of ITP for > 6 months in 9 of 9 cases (p < 0.0005); if only children with untreated de novo ITP (n = 20) were considered, 13 of 15 children with a normal polyploidization had an acute course of their ITP and 5 of 5 children with an impaired polyploidization developed chronic ITP (p < 0.003).

Conclusions: The results in this small group of patients suggest that the assessment of the relative size of the endomitotic compartment after 7 and 12 days in plasma clot culture actually appears to be the best method for predicting a chronic course in children with ITP.